European Journal of Inflammation (Sep 2022)
Erythropoietin-producing hepatocyte kinase receptor A1 facilitating the prgression of SGC-7901 cells and its transplanted tumor by increasing the expression of interleukin-6 and vascular endothelial growth factor in tumor microenvironment
Abstract
Objectives Many researches showed that Erythropoietin-producing hepatocyte kinase receptor A1 (EphA1) can promote the occurrence and development of malignant tumors and may be related to tumor microenvironment. But most of them are phenomenon studies, and there are few in-depth and complete mechanism studies. This study aims to understand how EphA1 promotes the progression of malignant tumors by regulating tumor microenvironment (focusing on Interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF)) from two experimental dimensions of in vitro and in vivo by using genetic engineering technology. Material and Methods We used genetic engineering technology to enhance and knock down EphA1 gene expression in SGC-7901 cells, respectively, and analyzed its influence on cell function and the expression levels of VEGF and IL-6 in cells. Subsequently, we constructed human EphA1 gene overexpression, EphA1 gene silencing, and normal expression of human EphA1 gene subcutaneous transplanted tumor models of SGC-7901 cells nude mice, and analyzed the differences in tumor development and the changes in the expression levels of VEGF and ILl-6 in tumor tissues. Results After EphA1 gene expression was enhanced, the proliferation, invasion and migration of SGC-7901 cells were enhanced, and apoptosis was weakened, and the expression levels of VEGF and IL-6 were increased. While the opposite results were found when EphA1 gene expression were knocked down. Meanwhile, tumor formation time and growth rate of subcutaneous transplantation in nude mice were advanced and the expression levels of VEGF and IL-6 in tumor tissues were increased when EphA1 gene expression were overexpressed by genetic engineering technology. Similarly, the opposite effect occurred in transplanted tumor model when EphA1 gene was silenced. Conclusion Our study showed that EphA1 can up-regulating VEGF and IL-6 expression, thereby enhancing the inflammatory environment and angiogenesis in the tumor microenvironment, and this helps to promote the progression of SGC-7901 cells and its transplanted tumor.